4-176686027-T-C

Position:

• chr4-176686027-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005429.5(VEGFC):​c.1145+1160A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,080 control chromosomes in the GnomAD database, including 30,840 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (30840 hom., cov: 33)
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123

Genes affected

VEGFC (HGNC:12682): (vascular endothelial growth factor C) The protein encoded by this gene is a member of the platelet-derived growth factor/vascular endothelial growth factor (PDGF/VEGF) family. The encoded protein promotes angiogenesis and endothelial cell growth, and can also affect the permeability of blood vessels. The proprotein is further cleaved into a fully processed form that can bind and activate VEGFR-2 and VEGFR-3 receptors. [provided by RefSeq, Apr 2014]

HAFML (HGNC:56694): (HuR (ELAVL1) associated fibroblast migratory lncRNA)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VEGFC	NM_005429.5	c.1145+1160A>G		intron_variant		ENST00000618562.2
HAFML	NR_183975.1	n.182+16318T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VEGFC	ENST00000618562.2	c.1145+1160A>G		intron_variant		1	NM_005429.5	P1
HAFML	ENST00000509194.1	n.89+16318T>C		intron_variant, non_coding_transcript_variant		3
HAFML	ENST00000504017.5	n.140+6277T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95172 AN: 151962 Hom.: 30841 Cov.: 33

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.630

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.626 AC: 95211 AN: 152080 Hom.: 30840 Cov.: 33 AF XY: 0.634 AC XY: 47118 AN XY: 74358

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.686

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.738

Gnomad4 FIN AF: 0.752

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.628

Alfa AF: 0.634 Hom.: 5578

Bravo AF: 0.604

Asia WGS AF: 0.707 AC: 2455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7665213; hg19: chr4-177607181;